Is Afamin a novel biomarker for gestational diabetes mellitus? A pilot study

Abstract

BackgroundIn search of potential early biomarkers for timely prediction of gestational diabetes mellitus (GDM), we focused on afamin, a vitamin E–binding protein in human plasma.. Afamin plays a role in anti-apoptotic cellular processes related to oxidative stress and is associated with insulin resistance and other features of metabolic syndrome. During uncomplicated pregnancy its serum concentrations increase linearly. The aim of this study was to investigate the suitability of afamin as early marker for predicting GDM.MethodsIn a first-trimester cohort from a prospective observational study of adverse pregnancy outcomes we secondarily analyzed afamin concentrations in 59 patients diagnosed with GDM and 51 controls. Additionally, afamin concentrations were cross-sectionally examined in a mid-trimester cohort of 105 women and compared with results from a simultaneously performed oral glucose tolerance test (OGTT). Subgroup analysis comparing patients treated with either insulin (iGDM) or dietary intervention (dGDM) was performed in both cohorts. Patients were recruited at the University Hospital Essen, Germany, between 2003 and 2016.ResultsResults were adjusted for body-mass-index (BMI) and gestational age. First and mid-trimester cohorts yielded significantly elevated afamin concentrations in patients with pathological OGTT compared to patients without GDM (first trimester cohort: mean, 113.4 mg/l; 95% CI, 106.4–120.5 mg/l and 87.2 mg/l; 95% CI, 79.7–94.7 mg/l; mid-trimester cohort: mean, 182.9 mg/l; 95% CI, 169.6–196.2 mg/l and 157.3 mg/l; 95% CI, 149.1–165.4 mg/l, respectively). In the first-trimester cohort, patients developing iGDM later in pregnancy presented with significantly higher afamin concentrations compared to patients developing dGDM and compared to patients without GDM. In the mid-trimester cohort, mean concentrations of afamin differed significantly between patients with dGDM compared to controls and between patients with iGDM and controls. Patients with iGDM showed only slightly higher afamin levels compared to patients with dGDM.ConclusionAfamin may serve as a new early biomarker for pathological glucose metabolism during pregnancy. Further research is needed to determine afamin’s concentrations during pregnancy, its predictive value for early detection of pregnancies at high risk to develop GDM and its diagnostic role during the second trimester.

Afamin: an early predictor of preeclampsia

“…In accordance with the previous studies of our working group [ 19 , 21 ], we found generally higher afamin concentrations in pregnant as well as in non-pregnant women compared to other study cohorts. This phenomenon remains somehow inexplicable and we hypothesise that ethnic differences might contribute to the higher concentrations in our study population.…”

“…A recently published population-based study including more than 20,000 individuals demonstrated elevated afamin concentrations in individuals with type 2 diabetes mellitus (T2DM) and IR [ 18 ]. Serum afamin concentrations are elevated in patients with polycystic ovarian syndrome (PCOS) and IR [ 19 , 20 ] and in the first trimester of women developing subsequent gestational diabetes mellitus [ 21 , 22 ]. These observations agree with the results of several studies that have suggested cross-links between oxidative stress, the insulin pathway, chronic inflammation and endothelial dysfunction in the pathogenesis of PE [ 23 – 26 ].…”

Molecular pathophysiology of diabetes mellitus during pregnancy with antenatal complications

“…It has recently been demonstrated that the AFM level was significantly lower in women with uncomplicated pregnancy compared to those with pre-eclampsia (1.2 folds change, p = 0.007) 68 . A correlation between AFM with GDM progression has also been reported 71 whereupon an increased AFM expression was encouraged as an essential reference with high potency for pregnancy-related disorders 68,71 .…”

Afamin predicts gestational diabetes in polycystic ovary syndrome patients preconceptionally

“…In a previous study, we were able to demonstrate a strong association between IR and serum afamin concentrations in PCOS patients (19). Additionally, we demonstrated elevated afamin serum concentrations determined during the first and second trimester of pregnancy in patients with GDM (20).…”